Rotavirus spike protein \u0394VP8* as a novel carrier protein for conjugate vaccine platform with demonstrated antigenic potential for use as bivalent vaccine

Wook-Jin Park,Yeon-Kyung Yoon,Ji-Sun Park,Ravi Ganapathy,Ruchirkumar Pansuriya,Yeong-Jae Seok

doi:10.1038/s41598-021-01549-z

Wook-Jin Park, Yeon-Kyung Yoon + Show 4 more

Open Access

https://doi.org/10.1038/s41598-021-01549-z

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Abstract

Conjugate vaccine platform is a promising strategy to overcome the poor immunogenicity of bacterial polysaccharide antigens in infants and children. A carrier protein in conjugate vaccines works not only as an immune stimulator to polysaccharide, but also as an immunogen; with the latter generally not considered as a measured outcome in real world. Here, we probed the potential of a conjugate vaccine platform to induce enhanced immunogenicity of a truncated rotavirus spike protein ΔVP8*. ΔVP8* was covalently conjugated to Vi capsular polysaccharide (Vi) of Salmonella Typhi to develop a bivalent vaccine, termed Vi-ΔVP8*. Our results demonstrated that the Vi-ΔVP8* vaccine can induce specific immune responses against both antigens in immunized mice. The conjugate vaccine elicits high antibody titers and functional antibodies against S. Typhi and Rotavirus (RV) when compared to immunization with a single antigen. Together, these results indicate that Vi-ΔVP8* is a potent and immunogenic vaccine candidate, thus strengthening the potential of conjugate vaccine platform with enhanced immune responses to carrier protein, including ΔVP8*.

Highlights

Rotaviruses are a primary cause of acute gastroenteritis in infants and children under five years of age, resulting in 24 million outpatient visits, 2.3 million hospitalizations, and 200,000 deaths a nnually1–3
The results showed that the virulence capsular polysaccharide (Vi)-ΔVP8* conjugates induced significantly high immune response toward the ΔVP8* antigens and Vi polysaccharides, making it a promising multivalent vaccine candidate against multiple rotavirus P types and S
A carrier protein in conjugate vaccines serves as an immune stimulator to a covalently linked polysaccharide antigen, resulting in better immune response in infants and children44,45

Summary

Introduction

Rotaviruses are a primary cause of acute gastroenteritis in infants and children under five years of age, resulting in 24 million outpatient visits, 2.3 million hospitalizations, and 200,000 deaths a nnually. Among several licensed rotavirus vaccines, four live attenuated oral vaccines (RotaTeq, Rotarix, ROTAVAC and ROTASIIL) are currently included in national immunization schedules in >100 countries worldwide. Among several licensed rotavirus vaccines, four live attenuated oral vaccines (RotaTeq, Rotarix, ROTAVAC and ROTASIIL) are currently included in national immunization schedules in >100 countries worldwide4 While these vaccines have been highly effective with 80–90% efficacy shown in developed countries, their efficacies are impaired in low- and middle-income countries where rotavirus vaccines are mostly needed. Vaccines were developed to enhance the immunogenicity of natural carbohydrate antigens, which are considered T cell-independent, a carrier protein may induce an immune response against itself. The conjugate vaccine platform may induce protective immunity against the pathogen from which the polysaccharide is derived, and from which the carrier protein is derived. REPA and a rationally designed recombinant protein containing strings of universal C D4+ T-cell epitopes proved to be good candidates as carrier p roteins

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